An examination of CPK models of complexes of ethidium analogs with DNA, based on the structure of an ethidium-dinucleoside monophosphate crystalline complex determined by X-ray crystallography, leads us to propose synthesis of certain ethidium analogs. Models of derivatives with meta-substituents on the 6-phenyl ring of ethidium intercalate in the DNA helix with some base-sequence preference attained through hydrogen-bonding to specific sites in the helix. A second type of ethidium derivative is a "double-intercalator" comprising two phenanthridinium groups connected by a chain of a length most suitable for intercalation of each planar portion in a different site in the same helix or in two different helices. We plan to conduct basic biophysical studies to determine the validity of these predicted specificities and to obtain data useful for designing future intercalating compounds. A drug that binds selectively to DNA might be a more effective antitumor agent than is ethidium, which shows slight activity.